Germline PTEN mutation Cowden syndrome: an underappreciated form of hereditary kidney cancer.
Germline PTEN mutation Cowden syndrome: an underappreciated form of hereditary kidney cancer.
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DOI：
10.1016/j.juro.2013.06.012
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发表时间：
2013-12
影响因子：
6.6
通讯作者：
Linehan, W. Marston
中科院分区：
文献类型：
--
作者：
Shuch, Brian;Ricketts, Christopher J.;Vocke, Cathy D.;Komiya, Takefumi;Middelton, Lindsay A.;Kauffman, Eric C.;Merino, Maria J.;Metwalli, Adam R.;Dennis, Phillip;Linehan, W. Marston
Cowden综合征（CS）是一种与PTEN生殖系突变相关的遗传性癌症综合征。患者易患多种恶性肿瘤，包括肾细胞癌（RCC）。作为临床方案的一部分，对CS患者进行了评价。有肾细胞癌病史的患者进行了临床特征、肿瘤特征和家族史的回顾。对肾肿瘤进行杂合性缺失（洛）评价。在24例CS患者中，4例被确定为RCC（16.7%）。3例患者为孤立性肿瘤，2例为乳头状I型组织学，1例为透明细胞组织学。第4例患者为双侧同步性嫌色细胞瘤。没有患者有RCC的既往家族史。所有RCC患者均有CS的皮肤病学表现和大头畸形。在4例（80%）肿瘤中发现了PTEN突变的洛缺失。没有发现基因型-表型相关性，因为在不同的RCC组织学中发现了相同的突变。RCC是CS的一个未被充分认识的特征。由于大多数患者缺乏既往家族史或独特的RCC组织学，因此相关非肾脏特征的识别应针对遗传咨询的转介。PTEN洛缺失在CS肾肿瘤中常见。由于PTEN的缺失可以激活mTOR，并且mTOR抑制剂被FDA批准用于治疗RCC，因此这些药物在与CS相关的RCC中具有临床潜力。
Cowden syndrome (CS) is a hereditary cancer syndrome associated with a germline mutation in PTEN. Patients are predisposed to multiple malignancies including renal cell carcinoma (RCC). Patients with CS were evaluated as part of a clinical protocol. Those with a history of RCC underwent review of clinical features, tumor characteristics, and family history. Renal tumors were evaluated for loss of heterozygosity (LOH). Among 24 CS patients, 4 were identified with RCC (16.7%). Three patients had solitary tumors, two with papillary type I histology and one with clear cell histology. The fourth patient had bilateral, synchronous chromophobe tumors. No patients had a prior family history of RCC. All RCC patients had dermatologic manifestations of CS and had macrocephaly. LOH at the PTEN mutation was identified in 4 tumors (80%). No genotype-phenotype association was found, as the same mutation was identified in different RCC histologies. RCC is an underappreciated feature of CS. As most patients lack a prior family history or a distinctive RCC histology, recognition of the associated non-renal features should target referral for genetic counseling. PTEN LOH is common in CS renal tumors. Because loss of PTEN can activate mTOR and mTOR inhibitors are FDA-approved to treat RCC, these agents have clinical potential in RCC associated with CS.
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DOI：
10.1038/nrurol.2010.47
发表时间：
2010-05
期刊：
Nature reviews. Urology
影响因子：
--
作者：
通讯作者：
--
影响因子：
2.1
作者：
Mester JL;Zhou M;Prescott N;Eng C
通讯作者：
Eng C
影响因子：
64.8
作者：
Bertolotto, Corine;Lesueur, Fabienne;Bressac-de Paillerets, Brigitte
通讯作者：
Bressac-de Paillerets, Brigitte
影响因子：
6.2
作者：
Abou Youssif, Tamer;Fahmy, Mona Alam;Sircar, Kanishka
通讯作者：
Sircar, Kanishka
影响因子：
9.8
作者：
Vanharanta, S;Buchta, M;Eng, C
通讯作者：
Eng, C